Didemnin B (Synonyms: NSC 325319, NSC 333841) |
Catalog No.GC49153
One-Click Copy Product Info
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Didemnin B is a cyclic depsipeptide marine natural product with cytotoxicity.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 77327-05-0
Sample solution is provided at 25 µL, 10mM.
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Didemnin B is a cyclic depsipeptide marine natural product with cytotoxicity. Didemnin B binds to eukaryotic elongation factor eEF1A and acts on the 80S ribosomal complex to block protein synthesis. Didemnin B also inhibits RNA and DNA synthesis. Didemnin B can be used in research related to tumors, viral infections, and immunosuppression[1-4].
In vitro, HL-60 cells were treated with 1µM Didemnin B for 1-4 hours. Didemnin B induced apoptosis in HL-60 cells[5]. Human promyelocytic leukemia HL-60 cells were treated with 1µM Didemnin B for 2 hours. Didemnin B caused apoptotic morphology including nuclear condensation, nuclear fragmentation and membrane blebbing, and increased cytoplasmic double-stranded DNA fragment levels[6]. HL-60, Daudi, Namalwa, BL-29, Naliaka, FDC-P1, Molt-4, Jurkat, and MM96 cells were treated with 1µM Didemnin B for 2-12 hours. Didemnin B induced apoptosis in these cell lines[7].
In vivo, B6C3F1 mice were intraperitoneally injected with 320-1280μg/kg Didemnin B. Blood radioactivity peaked at 1 hour and then declined rapidly. Didemnin B persistently accumulated in the pancreas[8]. Leptin-deficient C57BL/6J mice fed an AIN-76A semipurified diet for 4 weeks were intraperitoneally injected with 50μg/kg Didemnin B on days 1, 4, and 7 of week 5. Didemnin B reduced food intake, liver weight and liver triglycerides, and improved fasting glucose, oral glucose tolerance, fasting insulin and insulin tolerance[9]. HRS/J hairless mice with cutaneous herpes simplex virus type 1 (HSV-1) infection on the lumbar skin were topically treated with Didemnin B (1.5μg per application; 3 times daily for 5 consecutive days) at the infection site. Didemnin B reduced mean lesion scores and improved survival curve survival rates[10].
References:
[1] Chun HG, Davies B, Hoth D, et al. Didemnin B. The first marine compound entering clinical trials as an antineoplastic agent. Invest New Drugs. 1986;4(3):279-84.
[2] Shin DM, Holoye PY, Forman A, et al. Phase II clinical trial of didemnin B in previously treated small cell lung cancer. Invest New Drugs. 1994;12(3):243-9.
[3] SirDeshpande BV, Toogood PL. Mechanism of protein synthesis inhibition by didemnin B in vitro. Biochemistry. 1995 Jul 18;34(28):9177-84.
[4] Li LH, Timmins LG, Wallace TL, et al. Mechanism of action of didemnin B, a depsipeptide from the sea. Cancer Lett. 1984 Jul;23(3):279-88.
[5] Johnson KL, Lawen A. Rapamycin inhibits didemnin B-induced apoptosis in human HL-60 cells: Evidence for the possible involvement of FK506-binding protein 25. Immunology and Cell Biology. 1999;77(3):242-8.
[6] Grubb DR, Wolvetang EJ, Lawen A. Didemnin B induces cell death by apoptosis: the fastest induction of apoptosis ever described. Biochemical and Biophysical Research Communications. 1995 Oct 24;215(3):1130-6.
[7] Baker MA, Grubb DR, Lawen A. Didemnin B induces apoptosis in proliferating but not resting peripheral blood mononuclear cells. Apoptosis. 2002;7(5):407-12.
[8] Beasley VR, Bruno SJ, Burner JS, et al. Fate of tritiated didemnin B in mice: excretion and tissue concentrations after an intraperitoneal dose. Biopharmaceutics & Drug Disposition. 2005;26(7):341-51.
[9] Hetherington AM, Sawyez CG, Sutherland BG, et al. Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic lipotoxicity in obese mice. Physiological Reports. 2016 Sep;4(17):e12963.
[10] Weed SD, Stringfellow DA. Didemnins A and B. Effectiveness against cutaneous herpes simplex virus in mice. Antiviral Research. 1983;3(5):269-74.
| Cell experiment [1]: | |
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Cell lines |
HL-60 cells (human promyeloid leukemia cell line) |
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Preparation Method |
HL-60 cells were maintained in RPMI-1640 supplemented with 10% heat-inactivated foetal calf serum, 100U/mL penicillin, 100μg/mL streptomycin, 1mM sodium pyruvate, 2mM L-glutamine and 5mM HEPES at 37°C, 5% CO2. Cells were treated with 1μM Didemnin B for up to 4 hours. After treatment, apoptotic morphology was assessed by cytospin, ethanol/acetic acid fixation, DAPI nuclear staining and light/UV microscopy counting of ≥400 cells per slide; enucleated HL-60 cytoplasts were prepared by discontinuous Ficoll/cytochalasin B gradient ultracentrifugation and treated with 1μmol/L Didemnin B for 3 hours or 5μM staurosporine for 4 hours, with phase-contrast microscopy for membrane blebbing. |
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Reaction Conditions |
1μM; 1h to 4h |
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Applications |
Didemnin B induced nuclear condensation, nuclear fragmentation and membrane blebbing in intact HL-60 cells, and did not induce apoptotic morphology in enucleated HL-60 cytoplasts, while staurosporine induced apoptotic morphology in both intact cells and cytoplasts. |
| Animal experiment [2]: | |
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Animal models |
5-week-old male leptin-deficient ob/ob mice on C57BL/6J background (and lean C57BL/6J controls) |
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Preparation Method |
Mice were fed AIN-76A semipurified diet ad libitum for 4 weeks. During week 5, mice received intraperitoneal injections of 50μg/kg Didemnin B (solubilized in 1% DMSO, 5.2% PEG400, 5.2% Tween 80, 88.6% sterile saline) on days 1, 4, and 7. A pair-fed vehicle group matched for food intake was included. On day 8, after a 6h fast, oral glucose tolerance test (1g/kg D-glucose) and insulin tolerance test (0.6IU/kg i.p.) were performed; mice were then sacrificed. Liver weight, epididymal fat weight, liver lipids, H&E and Oil Red O histology (NAFLD activity score), plasma ALT/AST, liver immunoblots (EEF1A1, GRP78, p-JNK, JNK, p-eIF2α, eIF2α, albumin, actin), qPCR for Xbp1s/Mcp1/Tnfa/Fgf21/Ldlr/Bsep/Apoa1 etc., FPLC plasma lipoprotein profile, and pancreatic insulin IHC were assessed. |
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Dosage form |
50μg/kg; i.p.; 3 injections on days 1, 4, 7 of week 5 |
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Applications |
Didemnin B reduced food intake, reduced liver weight, reduced liver triglyceride, reduced Oil Red O lipid droplets, reduced lobular inflammation score and total NAFLD activity score, reduced plasma ALT and AST, reduced hepatic GRP78 protein and p-JNK, downregulated hepatic Xbp1s, Mcp1 and Tnfa mRNA, normalized plasma triglyceride, total cholesterol and LDL cholesterol, restored VLDL-triglyceride and LDL-cholesterol FPLC peaks, improved oral glucose tolerance and insulin tolerance and fasting glucose/insulin to lean levels, and did not alter pancreatic islet area or size distribution versus ob/ob vehicle. |
References: [1] Johnson KL, Lawen A. Rapamycin inhibits didemnin B-induced apoptosis in human HL-60 cells: Evidence for the possible involvement of FK506-binding protein 25. Immunology and Cell Biology. 1999;77(3):242-8. [2] Hetherington AM, Sawyez CG, Sutherland BG, et al. Treatment with didemnin B, an elongation factor 1A inhibitor, improves hepatic lipotoxicity in obese mice. Physiological Reports. 2016 Sep;4(17):e12963. | |
| Cas No. | 77327-05-0 | SDF | |
| Synonyms | NSC 325319, NSC 333841 | ||
| Canonical SMILES | O=C1N2[C@](CCC2)([H])C(N([C@H](C(O[C@@H]([C@@H](C(N[C@]([C@H](CC(O[C@H](C([C@@H](C(N[C@H]1CC(C)C)=O)C)=O)C(C)C)=O)O)([H])[C@@H](C)CC)=O)NC([C@@H](CC(C)C)N(C)C([C@H]3N(C([C@@H](O)C)=O)CCC3)=O)=O)C)=O)CC4=CC=C(C=C4)OC)C)=O | ||
| Formula | C57H89N7O15 | M.Wt | 1112.4 |
| Solubility | Acetonitrile: 1 mg/ml | Storage | Store at -20°C |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 899 μL | 4.4948 mL | 8.9896 mL |
| 5 mM | 179.8 μL | 899 μL | 1.7979 mL |
| 10 mM | 89.9 μL | 449.5 μL | 899 μL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A crystalline solid
- COA (Certificate of Analysis)
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- Datasheet
Average Rating: 5 (Based on Reviews and 14 reference(s) in Google Scholar.)